Jun-Han Lee1, Joseph H Jeong2, Tae-Hwan Kim1, So-Yeon Kim1, Kyung-Eun Kim3, Je Kyung Seong2, Sang Hyuk Lee1. 1. Department of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. 2. Department of Developmental Biology and Genomics, College of Veterinary Medicine, Korea Mouse Phenotyping Center, Seoul National University, Seoul, Korea. 3. Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Abstract
BACKGROUND: Salivary gland neoplasms are relatively rare and comprise only 1%-4% of all human neoplasms. Salivary gland neoplasms also show an extremely wide range of morphological diversity. Currently, the genetic alterations and corresponding molecular mechanisms underlying salivary gland neoplasms development remain largely unknown. METHOD: We generated an inducible Tet-MAP3K8::MMTV-rTA mouse model by crossing the MAP3K8 transgenic mice with MMTR-rTA transgenic mice to express MAP3K8 in the salivary gland. RESULTS: MAP3K8 overexpression in the murine salivary glands of Tet-MAP3K8::MMTR-rTA transgenic mice induces tumorigenesis. Pathological investigations reveal partial fibrosis and adenosis of salivary glands, and foci of atypical squamoid cellular proliferation, which represent invasive squamous cell carcinoma (SCC). CONCLUSION: MAP3K8 overexpression is associated with SCC development in murine salivary glands. It provides an in vivo framework for the understanding of molecular mechanisms underlying SCC development in the salivary glands and also for the development of a future therapeutic strategy targeting this tumor type.
BACKGROUND:Salivary gland neoplasms are relatively rare and comprise only 1%-4% of all humanneoplasms. Salivary gland neoplasms also show an extremely wide range of morphological diversity. Currently, the genetic alterations and corresponding molecular mechanisms underlying salivary gland neoplasms development remain largely unknown. METHOD: We generated an inducible Tet-MAP3K8::MMTV-rTAmouse model by crossing the MAP3K8transgenic mice with MMTR-rTAtransgenic mice to express MAP3K8 in the salivary gland. RESULTS:MAP3K8 overexpression in the murine salivary glands of Tet-MAP3K8::MMTR-rTAtransgenic mice induces tumorigenesis. Pathological investigations reveal partial fibrosis and adenosis of salivary glands, and foci of atypical squamoid cellular proliferation, which represent invasive squamous cell carcinoma (SCC). CONCLUSION:MAP3K8 overexpression is associated with SCC development in murine salivary glands. It provides an in vivo framework for the understanding of molecular mechanisms underlying SCC development in the salivary glands and also for the development of a future therapeutic strategy targeting this tumor type.